Wotton David, Pemberton Lucy F, Merrill-Schools Jacqueline
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, 22908, USA.
Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA, 22908, USA.
Adv Exp Med Biol. 2017;963:35-50. doi: 10.1007/978-3-319-50044-7_3.
Many of the known SUMO substrates are nuclear proteins, which regulate gene expression and chromatin dynamics. Sumoylation, in general, appears to correlate with decreased transcriptional activity, and in many cases modulation of the chromatin template is implicated. Sumoylation of the core histones is associated with transcriptional silencing, and transcription factor sumoylation can decrease gene expression by promoting recruitment of chromatin modifying enzymes. Additionally, sumoylation of transcriptional corepressors and chromatin remodeling enzymes can influence interactions with other transcriptional regulators, and alter their enzymatic activity. In some cases, proteins that are components of transcriptional corepressor complexes have been shown to be SUMO E3 ligases, further emphasizing the integration of sumoylation with the regulation of chromatin remodeling. Despite the evidence suggesting that sumoylation is primarily repressive for access to chromatin, recent analyses suggest that protein sumoylation on the chromatin template may play important roles at highly expressed genes. Elucidating the dynamic interplay of sumoylation with other post-translational modifications of histones and chromatin associated proteins will be key to fully understanding the regulation of access to the chromatin template.
许多已知的SUMO底物是核蛋白,它们调节基因表达和染色质动态变化。一般来说,SUMO化似乎与转录活性降低相关,并且在许多情况下涉及染色质模板的调节。核心组蛋白的SUMO化与转录沉默相关,转录因子的SUMO化可通过促进染色质修饰酶的募集来降低基因表达。此外,转录共抑制因子和染色质重塑酶的SUMO化可影响与其他转录调节因子的相互作用,并改变它们的酶活性。在某些情况下,已证明作为转录共抑制复合物成分的蛋白质是SUMO E3连接酶,这进一步强调了SUMO化与染色质重塑调节的整合。尽管有证据表明SUMO化主要对染色质的可及性起抑制作用,但最近的分析表明,染色质模板上的蛋白质SUMO化可能在高表达基因中起重要作用。阐明SUMO化与组蛋白和染色质相关蛋白的其他翻译后修饰之间的动态相互作用,将是全面理解染色质模板可及性调节的关键。